a) Field of the Invention
This invention relates to a method for freeze-drying of foodstuffs, medicaments, etc. to obtain such products in their desiccated form by first adjusting the starting materials for such foodstuffs, medicaments, etc. in their liquid form, and then freeze-drying such liquid material into the final desiccated powder products. This invention is also concerned with a system for attaining such freeze-drying of foodstuffs, medicaments, and so forth.
b) Description of Prior Arts
Conventionally, the system for freeze-drying (or lyophilizing) foodstuffs, medicaments, etc., by which the materials therefor in liquid form are subjected to freeze-drying through sublimation heat supplied under the vacuum condition, is usually constructed in such a manner that the material to be dried is filled, in its liquid form, in a desiccating vessel such as tray, and the like, then such tray with the material to be dried is placed in a desiccating chamber of a freeze-drying device provided with a stack of shelves, thereafter the material is freeze-dried in bulk form, and, after drying, the material as dried is comminuted by a pulverizer, the final product in powder form being collected into a receptacle.
More concretely, this conventional freeze-drying apparatus is made up of the following elements, taking a currently implemented apparatus for the production of medicaments, as an example. That is to say, referring to FIG. 1 of the accompanying drawing, a block enclosed by a double-dot-and-dash line (I) designates an apparatus A for adjusting starting materials, which performs a step of adjusting the starting materials into a liquid form (it being understood that, throughout this description, xe2x80x98slurryxe2x80x99 will also be included in this category of liquid material). This materials adjusting apparatus A is constituted with a plurality of mutually juxtaposed blending tanks a, a, . . . and an adjusting tank b. A predetermined quantity of such starting material as weighed is poured by human hands into the blending tanks a, a, . . . , together with a solvent (distilled water) through the charging port 10 of each of them, followed by operating agitators 11, 11, . . . installed in the blending tanks a, a, . . . by means of motors 12, 12, . . . equipped on each agitator, thereby effecting blending of the materials, as charged, through agitation to cause the starting materials and the solvent to be made into a liquid material. This liquid material is then charged into the adjusting tank b through a charging port 20 of the adjusting tank b by human hands, while, at the same time, a predetermined quantity of the solvent (distilled water) is further poured therein. Subsequently, an agitator 21 installed in the adjusting tank b is operated by a motor 22 to blend the materials in liquid form by agitation to adjust it into the liquid material of a predetermined composition. As soon as this adjusting operation is completed, the liquid material as adjusted is let out of the discharge port 23 at the bottom of the adjusting tank b by the action of a pump P connected to the discharge port 23 through a pipeline. It should be noted that this liquid material as adjusted is transferred to the subsequent step of xe2x80x98distributive pouringxe2x80x99 through a pipeline c provided with a sterilized filter and connected to the discharge port of the pump P.
Again, in reference to FIG. 1, a block enclosed by a double-dot-and-dash line (II) designates the distributive pouring (or feeding) apparatus B which performs the distributive pouring step to distribute the liquid material as adjusted in the abovementioned step of adjusting the materials. This distributive pouring apparatus is constituted with a distributive pouring tank d connected to the downstream side of the abovementioned pipeline c; a pipeline 31 for the distributive pouring, connected to its discharge port through a sterilized filter 30; and a loading device (not shown in the drawing) which is disposed below the discharge port 32 of the pipeline 31 so as to sequentially carry into, or carry out, a desiccating vessel e, such as tray, etc., into which the liquid material to be discharged from the distributive pipeline 31 is poured; and so forth.
In this figure of drawing, a block surrounded by a double-dot-and-dash line (III) refers to a freeze-drying apparatus C to perform the freeze-drying of the liquid material. This freeze-drying apparatus comprises a freeze-drying device f with stack of shelves, which functions to introduce the desiccating vessels e, e, . . . , each being filled with the liquid material, into the desiccating chamber for its freeze-drying. In the front face 40 of the storage chamber for the freeze-drying device f, there is formed, in a freely openable and closable manner, an opening 41, through which the desiccating vessels e, e, . . . are introduced into, or taken out of, the freeze-drying apparatus. Further, in the front face side of the opening 41, there is provided the loading apparatus (not shown in the drawing) for performing the introduction and removal of the desiccating vessels e, e, . . . , each being filled with the liquid material. In addition, an isolating device or an isolator (not shown in the drawing) for preventing contamination is provided between the blocks (II) and (III).
In the same drawing, a block surrounded by a double-dot-and-dash line (IV) designates a crushing and comminuting apparatus D which performs a step of crushing and pulverizing the desiccated product (in bulk) from the liquid material which has been subjected to the freeze-drying in the desiccating chamber 40 of the freeze-drying device f. This pulverizing apparatus D is constituted with a comminuting device g made up of a continuous series of: a power mill 51 to receive therein a bulk of the liquid material solidified in the desiccating vessels e, e, . . . through a hopper 50; a jet mill 52 for comminuting the crushed product; and a cyclone 53 which separates the comminuted product discharged from the jet mill 52 into powder and air. At the lower discharge port of the cyclone 53, there is disposed a receptacle h for receiving thereinto the powder product to be taken out of the discharge port. Further, in the vicinity of the hopper 50 of the comminuting device g, there is provided a loading device (not shown in the drawing), or a feeder device, for throwing into the hopper 50, the dried product which is solidified in the interior of the desiccating vessels e, e, . . . , into which the material to be dried has been transported.
In the same drawing, too, a block surrounded by a double-dot-and-dash line (V) designates a washing and sterilizing apparatus E for washing and sterilizing the desiccating vessels e, e, . . . which are used by filling the liquid material therein and loaded in the freeze-drying device f The washing and sterilizing device is constructed with the washing device i for washing the desiccating vessels e, e, . . . , and the sterilizing device j for sterilizing the desiccating vessels as washed. The loading apparatus (not shown in the drawing) is disposed at each of the charging ports and the take-out ports of the desiccating vessels e, e, . . . .
Thus, the final powder product is obtained by and through each of these blocks, i.e., the material adjusting step where the liquid material is adjusted by the material adjusting device A; distributive pouring (or feeding) step where the liquid material as adjusted in the preceding step is distributively fed into the desiccating vessels e, e, . . . which have been sterilized in the sterilizing step so as to fill the material in each of these vessels; the desiccating step where the desiccating vessels e, e, . . . filled with the liquid material are placed in the freeze-drying apparatus for freeze-drying of the liquid material; and the crushing (or grinding) step where the dried products (in bulk form) from the liquid material solidified in the desiccating vessels e, e, . . . are thrown into the comminuting device g to comminute the desiccated material into the final product in fine powder. Each of these process steps is effected in a clean room, where a ratio of the floating quantity of the minute particles is regulated. Furthermore, various operations such as the loading and removing of the desiccating vessels e, e, . . . , as washed, onto and from the sterilizing device j; the distributive pouring and filling of the liquid material into the desiccating vessels e, e, . . . ; the loading of the desiccating vessels e, e, . . . filled with the liquid material into the freeze-drying device f; the removing of the desiccating vessels e, e, . . . which have completed desiccation of the liquid material from the freeze-drying device; the removing of the dried product (in bulk form) of the liquid material from the desiccating vessels e, e, . . . , and the throwing of the dried product into the comminuting device g; the separation of the treated product, which has been subjected to comminution, into the final powder product and air, so as to take out the powder product alone; and other operations, are effected in clean booths k, k . . . , each of which encloses each and every operational space.
In the abovementioned means for making the powder product by adjusting the starting materials into the liquid material of a predetermined composition, desiccating the liquid material by the freeze-drying device, and comminuting the thus freeze-dried liquid material into the required powder product, since each of these process steps (i.e., material adjusting step, distributive feeding step, desiccating step, comminuting step, etc.) is independent of the other, and moreover, since human being or robot (manipulator) intervenes for carrying out the operations in each process step, there has been a problem such that it is troublesome to carry out each and every process step as well as connection of the adjacent process steps in the clean room satisfying various rules and regulations for the purpose of securing perfect sterilization of the ultimate powder product and of preventing the powder product from the risk of contamination from outside, which involves a great deal of investment for the construction of the facility.
The present invention has been made with a view to solving the above-described various problems inherent in the conventional system, and aims at providing improved means for enabling the sterilized condition of the powder product to be maintained as well as prevention of the risk of its contamination from the external atmosphere to be effectively secured. The invention is also to provide a novel expedient for enabling the entire process steps to be continuously operable in the form of a closed system. Such process steps can be realized in the freeze-drying system for obtaining an intended powder product through the process steps of: adjusting starting materials into a liquid form; distributively feeding the thus adjusted liquid material for its freeze-drying; desiccating the liquid material by the freeze-drying device; comminuting the thus desiccated liquid material by a comminuting device; and so forth, wherein the connected parts between the mutually adjacent process steps are brought to a condition, in which the continuous operations of the process step are made possible, thereby enabling the whole process steps to be isolated from the external atmosphere.
In view of the above-described points of problem, which are inherent in the conventional freeze-drying method and apparatus, it is a primary object of the present invention to provide a method for freeze-drying foodstuffs, medicaments, etc., which comprises steps of: adjusting starting materials and a solvent therefor into a liquid material by means of a material adjusting apparatus A made up of blending tanks a, a, . . . , an adjusting tank b, and so forth; introducing the liquid material into a shell 60 constituting a desiccating chamber of a shell-tube type freeze-drying device f through a pipeline c to immediately and distributively feed said liquid material into a plurality of tubes 61, 61, . . . which are juxtaposed each other in the upright position within the shell 60, to cause the liquid material to freeze in a tubular layer; and, after freeze-drying of the liquid material by a freeze-drying device, subjecting the thus freeze-dried tubular product, dropping from the tubes 61, 61, . . . within the shell 60, to the comminuting treatment by a comminuting device g into the ultimate powder product.
It is another object of the present invention to provide a method for freeze-drying foodstuffs, medicaments, etc., which comprises steps of: adjusting starting materials and a solvent therefor into a liquid material by means of a material adjusting apparatus A made up of blending tanks a, a, . . . , an adjusting tank b, and so forth; introducing the liquid material into a shell 60 constituting a desiccating chamber of a shell-tube type freeze-drying device f through a pipeline c to immediately and distributively feed the liquid material into a plurality of tubes 61, 61, . . . , which are juxtaposed each other in the upright position within the shell 60 to cause the liquid material to freeze in a tubular layer; and, after freeze-drying of the liquid material by the freeze-drying device, subjecting the thus freeze-dried tubular product, dropping from the tubes 61, 61, . . . within the shell 60, to the comminuting treatment by a crushing (grinding) device w disposed in a receptacle 72 for the desiccated product, placed below the shell 60 in continuation to this shell 60 while maintaining the vacuum condition; and forwarding the tubular desiccated product into a comminuting device g connected to the bottom surface side of the desiccated product receptacle 72 for the comminuting treatment to render the same to be the ultimate powder product.
It is still another object of the present invention to provide a freeze-drying apparatus for foodstuffs, medicaments, and so forth, which comprises: a distributor 80 for distributively feeding a liquid material into a plurality of tubes 61, 61, . . . above a shell 60 constituting a desiccating chamber of a shell-tube type freeze-drying device f, the tubes being juxtaposed each other in the upright position within the shell 60, the downstream side of the pipeline c to guide the liquid material from the adjusting tank b of the material adjusting apparatus A being connected to distributor 80 directly or through an atomizing nozzle.
It is other object of the present invention to provide a freeze-drying apparatus for foodstuffs, medicaments, and so forth, which comprises: an atomizing nozzle pipe 110 having a small diameter, which is disposed at the axial center position within the inner bore of a plurality of tubes 61, 61,. . . , which are juxtaposed each other in the upright position within the shell 60 constituting a desiccating chamber of a shell-tube type freeze-drying device f, a multitude of atomizing holes 111, 111, . . . being perforated in the cylindrical wall of the tubes, and the downstream side of the pipeline c to guide the liquid material from the adjusting tank b of the material adjusting apparatus A being connected to the upper end side of the atomizing nozzle pipes 110, 110, . . . , either directly or through the atomizing nozzle pipes.
It is still other object of the present invention to provide a freeze-drying apparatus for foodstuffs, medicaments, and so forth, which comprises: supporting rods 120, 120, . . . of a small diameter, which are disposed at the axial center position within each inner bore of a plurality of tubes 61, 61, . . . , which are juxtaposed each other in the upright position within the shell 60 constituting a desiccating chamber of a shell-tube type freeze-drying device, a small-sized holding rack 70b, formed in the shape of a opening-and-closing butterfly valve, to support the lower end side of the frozen layer of the liquid material, which has been subjected to the freeze-drying in a tubular shape within each of the tubes 61, 61, . . . , being supported onto each of the lower end parts of the supporting rods 120, 120, . . . , and an operating wire or pneumatically operated actuator for rotating these holding racks pneumatically operated actuator for rotating these holding racks 70, 70, . . . individually for their open and close actions being connected to each of the holding racks in the butterfly valve shape.
It is a further object of the present invention to provide a freeze-drying apparatus for foodstuffs, medicaments, and so forth, which comprises: a liquid material feeding tube 65, disposed at the lower surface side of the shell 60 constituting the desiccating chamber of the shell-tube type freeze-drying device f, the downstream side of which is communicatively connected to each of the lower end of a plurality of tubes 61, 61, . . . , which are juxtaposed each other in the upright position within the shell 60, the upstream side of this liquid material feeding tube 65 being connected and joined directly or through an atomizing nozzle, at the end part of the downstream side of the pipeline c which guides the liquid material from the adjusting tank b of the starting material adjusting apparatus A.
It is still further object of the present invention to provide a freeze-drying apparatus for foodstuffs, medicaments, and so forth, which comprises: a desiccated product receptacle 72 for receiving therein the desiccated product of the liquid material as dried by freezing the liquid material onto the wall surface of a plurality of tubes 61, 61, . . . , which are juxtaposed each other in the upright position within the shell 60, the desiccated product receptacle 72 being disposed below the shell 60 constituting the desiccating chamber of the shell-tube type freeze-drying device f, in a manner to be connected to said shell 60 and maintained in the vacuum condition; and a grinding device w for crushing the desiccated product falling into the desiccated product receptacle 72 from the tubes 61, 61, . . . within the shell 60, in the course of its falling or after its falling. freeze-drying apparatus for foodstuffs, medicaments, and so forth, which comprises: a desiccated product receptacle 72 for receiving therein the desiccated product of the liquid material as dried by freezing the liquid material onto the wall surface of a plurality of tubes 61, 61, . . . , which are juxtaposed each other in the upright position within the shell 60, the desiccated product receptacle 72 being disposed below the shell 60 constituting the desiccating chamber of the shell-tube type freeze-drying device f, in a manner to be connected to the shell 60 and maintained in the vacuum condition; and a crushing device w disposed in the desiccated product receptacle 72 for crushing the desiccated product dropping into the desiccated product receptacle 72 from the tubes 61, 61, . . . within the shell 60, the bottom surface side of said desiccated product receptacle 72 being air-tightly connected to the hopper 50 of the comminuting device g through a special valve 83 provided with a material forwarding device.
The foregoing objects, other objects as well as specific construction of the shell-tube type freeze-drying system according to the present invention will become more apparent and understandable from the following detailed description of the preferred embodiments thereof, when read in conjunction with the accompanying drawing.